Departamento de Quı́mica, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago 1058, Chile.
Centro Integrativo de Biologı́a y Quı́mica Aplicada (CIBQA), Universidad Bernardo O'Higgins, Santiago 8370854, Chile.
J Org Chem. 2020 Jul 17;85(14):9272-9280. doi: 10.1021/acs.joc.0c01272. Epub 2020 Jul 5.
The mechanism and selectivity of phosphine-catalyzed [3 + 2] and [3 + 3] annulations of azomethine imines and allenoates have been computationally studied. Exploration of the potential energy surface reveals that the cyclization step is a key step controlling the selectivity of the process. This contrasts with previous studies on related transformations where the initial nucleophilic addition involving the activated allenoate was found to exclusively control the regioselectivity of the transformation. Among the possible reaction pathways, the energetically low-lying reaction channel involves an intramolecular Michael addition leading to the experimentally observed [3 + 2] product. The factors controlling the observed regioselectivity have been quantitatively rationalized by means of state-of-the-art computational methods, namely, the activation strain model of reactivity in combination with the energy decomposition analysis.
我们运用计算化学的方法研究了亚胺叶立德与丙二烯酸酯的膦催化[3+2]和[3+3]环加成反应的机理和选择性。对势能面的研究揭示了环化步骤是控制反应选择性的关键步骤。这与先前关于相关转化的研究结果形成了鲜明的对比，在先前的研究中，涉及活化丙二烯酸酯的初始亲核加成被认为是唯一控制转化区域选择性的因素。在所研究的可能反应途径中，能量较低的反应通道涉及分子内迈克尔加成，从而得到实验观察到的[3+2]产物。我们运用最先进的计算方法，即反应活性的应变激活模型与能量分解分析相结合，对观察到的区域选择性的控制因素进行了定量的合理化解释。
